Cervical and lumbar total disc replacements - KCE

KCE REPORT 254

CERVICAL AND LUMBAR TOTAL DISC REPLACEMENTS

2015

www.kce.fgov.be

KCE REPORT 254 HEALTH TECHNOLOGY ASSESSMENT

CERVICAL AND LUMBAR TOTAL DISC REPLACEMENTS

KIRSTEN HOLDT HENNINGSEN, NANCY THIRY, CHRIS DE LAET, SABINE STORDEUR, CÉCILE CAMBERLIN

2015

www.kce.fgov.be

COLOPHON Title:

Cervical and lumbar total disc replacements

Authors:

Kirsten Holdt Henningsen (KCE), Nancy Thiry (KCE), Chris De Laet (KCE), Sabine Stordeur (KCE), Cécile Camberlin (KCE)

Project coordinator supervisor:

and

Senior

Sabine Stordeur (KCE)

Reviewers:

Frank Hulstaert (KCE), Raf Mertens (KCE), Lorena San Miguel (KCE)

External experts:

Michael Bruneau (Belgian Society of Neurosurgery (BSN) – Hôpital Erasme, Bruxelles), Philippe Claesen (Jessa Ziekenhuis), Geert Crombez (UGent), Bart Depreitere (UZ Leuven), Hendrik Fransen (AZ St-Lucas Gent), Patrick Galloo (Socialistische Mutualiteiten), Alphonse Lubansu (Hôpital Erasme Bruxelles), Germain Milbouw (CHR Namur), Henri Nielens (Cliniques universitaires Saint-Luc, Bruxelles), Valérie Noblesse (INAMI – RIZIV), Bart Poffyn (UZ Gent), Stéphane Sobczak (AXXON), Johan Van Lerbeirghe (SSBE Spine Society of Belgium), Jan Van Meirhaeghe (AZ St-Jan Brugge), Patrick Van Schaeybroeck (Imelda Ziekenhuis, Bonheiden), Peter Van Wambeke (UZ Leuven), Dominique Verhulst (ZNA Stuivenberg, Antwerpen), René Westhovens (UZ Leuven)

External validators:

Wilco Jacobs (The Health Scientist, The Netherlands), Christian Raftopoulos (Cliniques universitaires St-Luc), Matt Stevenson (University of Sheffield, The United Kingdom)

Acknowledgements:

UNAMEC (Fédération belge de l’industrie des technologies médicales – Belgische federatie van de industrie van de medische technologiëen), Nicolas Fairon (KCE): information specialist

Other reported interests:

Membership of a stakeholder group on which the results of this report could have an impact: Wilco Jacobs (member of various focused spinal surgery associations), Johan Van Lerbeirghe (SSBE), Michael Bruneau (Hôpital Erasme – Université Libre de Bruxelles) Owner of subscribed capital, options, shares or other financial instruments: Wilco Jacobs (Clinical Research consultancy The Health Scientist) Fees or other compensation for writing a publication or participating in its development: Wilco Jacobs (Scientific collaborator for systematic literature research about lumbar disc prostheses) Participation in scientific or experimental research as an initiator, principal investigator or researcher: Wilco Jacobs (Principal Investigator ZonMW funds with cofinancing from Medtronic Inc for minimal invasive lumbar fusion, Principal Investigator for systematic literature research about spine); Bart Poffyn (Head Researcher ‘MISS Anterior Approach Tumors fractures in spine’) Grants, fees or funds for a member of staff or another form of compensation for the execution of research: Wilco Jacobs (Fees from LUMC for collaboration to the guideline development about robot spinal surgery)

Layout:

Consultancy or employment for a company, an association or an organisation that may gain or lose financially due to the results of this report: Dominique Verhulst (DePuy Spine (Johnson & Johnson)) Payments to speak, training remuneration, subsidised travel or payment for participation at a conference: Christian Raftopoulos (Johnson & Johnson conferences); Jan Van Meirhaeghe Presidency or accountable function within an institution, association, department or other entity on which the results of this report could have an impact: Johan Van Lerbeirghe (president SSBC); Patrick Galloo (President Implants and Invasive Medical Devices Reimbursement Commission); Patrick Van Schaeybroeck (Vice-President Spine Society Belgium; BNSS, Board Member Belgian Neurosurgical Spine Society) Ine Verhulst, Joyce Grijseels

Disclaimer:



The external experts were consulted about a (preliminary) version of the scientific report. Their comments were discussed during meetings. They did not co-author the scientific report and did not necessarily agree with its content.



Subsequently, a (final) version was submitted to the validators. The validation of the report results from a consensus or a voting process between the validators. The validators did not co-author the scientific report and did not necessarily all three agree with its content.



Finally, this report has been approved by common assent by the Executive Board.



Only the KCE is responsible for errors or omissions that could persist. The policy recommendations are also under the full responsibility of the KCE.

Publication date:

16 December 2015 (2nd edition; 1st edition: 29 October 2015)

Domain:

NLM Classification:

Health Technology Assessment (HTA) Total Disc Replacement; Low Back Pain; Intervertebral Disc Degeneration; Cervical Vertebrae; Lumbar Vertebrae WE 740

Language:

English

Format:

Adobe® PDF™ (A4)

Legal depot:

D/2015/10.273/94

HTA Core Model:

The HTA Core Model ® developed within EUnetHTA (www.eunethta.eu), has been utilised when producing the contents and structure of this work. The following version of the Model was used: HTACoreModel2.1PublicDraft.

MeSH:

Use of the HTA Core Model does not guarantee the accuracy, completeness, quality or usefulness of any information or service produced or provided by using the Model. The EUnetHTA JA 2 has received funding from the European Union, in the framework of the Health Programme. ISSN:

2466-6459

Copyright:

KCE reports are published under a “by/nc/nd” Creative Commons Licence http://kce.fgov.be/content/about-copyrights-for-kce-reports.

How to refer to this document?

Holdt Henningsen K, Thiry N, De Laet C, Stordeur S, Camberlin C. Cervical and lumbar total disc replacements. Health Technology Assessment (HTA) Brussels: Belgian Health Care Knowledge Centre (KCE). 2015. KCE Reports 254. D/2015/10.273/94. This document is available on the website of the Belgian Health Care Knowledge Centre.

KCE Report 254

Total disc replacement

 TABLE OF CONTENTS LIST OF FIGURES ...............................................................................................................................................2 LIST OF TABLES .................................................................................................................................................3 LIST OF ABBREVIATIONS .................................................................................................................................4  SCIENTIFIC REPORT............................................................................................................................7 1 INTRODUCTION ....................................................................................................................................7 1.1 BACKGROUND ......................................................................................................................................7 1.2 SCOPE AND OBJECTIVES ...................................................................................................................8 2 CERVICAL TOTAL DISC REPLACEMENT ..........................................................................................9 2.1 HEALTH PROBLEMS ............................................................................................................................9 2.1.1 Population and condition ..........................................................................................................9 2.1.2 Existing treatments...................................................................................................................9 2.2 DESCRIPTION AND TECHNICAL CHARACTERISTICS......................................................................9 2.3 CURRENT USE....................................................................................................................................14 2.3.1 Methods..................................................................................................................................14 2.3.2 Results ...................................................................................................................................15 2.4 CLINICAL EFFECTIVENESS AND SAFETY .......................................................................................19 2.4.1 Methods..................................................................................................................................19 2.4.2 Results on Clinical Effectiveness ...........................................................................................23 2.4.3 Results on Safety ...................................................................................................................35 2.4.4 Discussion ..............................................................................................................................42 2.5 ECONOMIC EVALUATION ..................................................................................................................42 2.5.1 Introduction ............................................................................................................................42 2.5.2 Methods..................................................................................................................................43 2.5.3 Characteristics of the economic evaluations..........................................................................44 2.5.4 Results of the economic evaluations .....................................................................................48 2.5.5 Discussion ..............................................................................................................................50 3 LUMBAR TOTAL DISC REPLACEMENT ...........................................................................................51 3.1 HEALTH PROBLEMS ..........................................................................................................................51

1

2


3.2 3.3

3.4

3.5



LIST OF FIGURES

KCE Report 254

3.1.1 Population and condition ........................................................................................................51 3.1.2 Existing treatments.................................................................................................................51 DESCRIPTION AND TECHNICAL CHARACTERISTICS....................................................................51 CURRENT USE....................................................................................................................................56 3.3.1 Methods..................................................................................................................................56 3.3.2 Results ...................................................................................................................................56 CLINICAL EFFECTIVENESS AND SAFETY .......................................................................................60 3.4.1 Methods..................................................................................................................................60 3.4.2 Results on Clinical Effectiveness ...........................................................................................62 3.4.3 Results on Safety ...................................................................................................................67 3.4.4 Discussion ..............................................................................................................................69 ECONOMIC EVALUATION ..................................................................................................................70 3.5.1 Introduction ............................................................................................................................70 3.5.2 Methods..................................................................................................................................70 3.5.3 Characteristics of the economic evaluations..........................................................................72 3.5.4 Results of the economic evaluations .....................................................................................75 3.5.5 Discussion ..............................................................................................................................77 REFERENCES .....................................................................................................................................78

Figure 1 – Anatomy of the spine ...........................................................................................................................8 Figure 2 – Cervical total disc replacement: Age distribution per gender ............................................................16 Figure 3 – Number of cervical total disc replacement per hospital performing this technique in 2011 ..............17 Figure 4 – Number of cervical total disc replacements performed in 2011 per hospital district (‘arrondissement’) ...............................................................................................................................................18 Figure 5 – Functional status: 12-24 months NDI mean difference (cervical total disc replacement versus fusion)......................................................................................................................................................26 Figure 6 – Arm Pain: 12-24 months NRS/VAS mean difference (cervical total disc replacement versus fusion) .................................................................................................................................................................27 Figure 7 – Neck Pain: 12-24 months NRS/VAS mean difference (cervical total disc replacement versus fusion) .................................................................................................................................................................28

KCE Report 254


Figure 8 – Mobility: 12-24 months ROM mean difference (cervical total disc replacement versus fusion)........29 Figure 9 – Neurological outcomes: 12-24 months RR (cervical total disc replacement versus fusion) .............30 Figure 10 – Revision surgery at index level: 12-24 months RR (cervical total disc replacement versus fusion) .................................................................................................................................................................36 Figure 11 – Secondary surgery at adjacent levels: 12-24 months RR (cervical total disc replacement versus fusion) .................................................................................................................................................................37 Figure 12 – Overall revision surgery rate: ≥48 months RR (cervical total disc replacement versus fusion) ......38 Figure 13 – Adjacent segment degeneration: ≥48 months RR (cervical total disc replacement versus fusion) .................................................................................................................................................................39 Figure 14 – Lumbar total disc replacement: Age distribution per gender ...........................................................57 Figure 15 – Number of lumbar total disc replacement per hospital performing this technique in 2011 .............58 Figure 16 – Number of lumbar total disc replacements performed in 2011 per hospital district (‘arrondissement’) ...............................................................................................................................................59

LIST OF TABLES

Table 1 – List of main cervical artificial discs available in Belgium ....................................................................12 Table 2 – Pictures of main cervical artificial discs widely available in Belgium ..................................................13 Table 3 – Number of cervical artificial discs or cervical total disc replacements by data source .......................15 Table 4 – PICO table and selection criteria for cervical total disc replacement .................................................20 Table 5 – Description of selected assessment instruments used in included studies ........................................21 Table 6 – Base-case characteristics of the full economic evaluations of cervical total disc replacement..........45 Table 7 – Results of the full economic evaluations of cervical total disc replacement .......................................49 Table 8 – Results of the incremental analysis from Lewis et al., 201455 ............................................................49 Table 9 – List of lumbar artificial discs reimbursed in Belgium ...........................................................................53 Table 10 – Pictures of main lumbar artificial discs available in Belgium ............................................................54 Table 11 – Number of lumbar artificial discs or lumbar total disc replacement by data source .........................56 Table 12 – INAMI – RIZIV reimbursed amounts for lumbar artificial discs (€) ...................................................57 Table 13 – PICO table and selection criteria for lumbar total disc replacement.................................................61 Table 14 – Base-case characteristics of the full economic evaluations of lumbar total disc replacement .........72 Table 15 – Results of the full economic evaluations of lumbar total disc replacement ......................................76

3

4


LIST OF ABBREVIATIONS

KCE Report 254

ABBREVIATION

DEFINITION

95% CI ACD ACDF ALIF ASD ASP CBA CEA CLBP CMA Co Cr CRD CTDR CUA DCRA DDD DGSIE – ADSEI EQ-5D FA

95% confidence interval Anterior cervical discectomy (no fusion) Anterior cervical discectomy and fusion Anterior lumbar interbody fusion Adjacent segment degeneration Adjacent segment pathology Cost-benefit analysis Cost-effectiveness analysis Chronic low back pain Cost-minimization analysis Cobalt Chromium Centre for Review and Dissemination Cervical total disc replacement Cost-utility analysis Distortion compensated röntgen analysis Degenerative disc disease Direction générale Statistique et Information économique – Algemene Directie Statistiek en Economische Informatie - Statistics Belgium EuroQoL 5 dimensions Facet arthropathy

FDA

Food and Drug Administration (USA)

HCP HRQoL HTA HUI

Health care payer Health Related Quality of Life Health Technology Assessment Health Utilities Index

KCE Report 254


ICER ICD-9-CM INAMI – RIZIV INAHTA LBP LOS LTDR LY MD MCID Mo NDI NHS EED NICE NRS NSAID ODI OR PICO PLIF PLF PMMA QALY QoL QWB RCT RHM – MZG RMDQ

5

Incremental cost-effectiveness ratio International Classification of Diseases, Ninth Revision, Clinical Modification Institut national d'assurance maladie-invalidité - RijksInstituut voor ziekte en invaliditeits verzekering (Belgium) International Network of Agencies for Health Technology Assessment Low back pain Length of stay Lumbar total disc replacement Life year Mean difference Minimally clinically important difference Molybdenum Neck Disability Index National Health Service Economic Evaluation Database National Institute for Health and Care Excellence (UK) Numeric Rating Scale Non-steroidal anti-inflammatory drug Oswestry Disability Index Odds ratio Patient, Intervention, Comparator, Outcomes Posterior lumbar interbody fusion Posterolateral lumbar fusion Polymethylmetacrylat Quality-adjusted life year Quality of life Quality of Well-Being scale Randomised controlled trial Résumé Hospitalier Minimum – Minimum Ziekenhuisgegevens Rolland Morris Disability Questionnaire

6


KCE Report 254

ROM RR SA SD

Range of motion Relative risk Sensitivity analysis Standard deviation

SF-6D

Short Form-6 dimension

SF-12

Short Form-12 (items)

SF-36

Medical Outcome Study Short Form 36-Item Health Survey

SMD

Standardized mean difference

SPF – FOD

Service Public Fédéral Santé publique, Sécurité de la Chaîne alimentaire et Environnement – Federale Overheidsdienst Volksgezondheid, Veiligheid van de Voedselketen en Leefmilieu Total disc replacement Titanium Ultra-high molecular weight polyethylene Visual Analog Scale Extreme lateral interbody fusion

TDR Ti UHMWPE VAS XLIF

KCE Report 254

 SCIENTIFIC REPORT


7

1 INTRODUCTION 1.1

Background

The human spine comprises 33 vertebrae grouped according to their location: 7 cervical (numbered C1-C7), 12 thoracic (T1-T12), 5 lumbar (L1L5), 5 sacral (S1-S5) and four coccygeal ones. The sacral and coccygeal vertebrae are fixed but the other vertebrae are said movable. Vertebrae C2 to S1 are separated by each other by an intervertebral disc made of a fibrocartilaginous annulus fibrosis surrounding a soft pulpy semi-gelatinous core: the nucleus pulposus. These intervertebral discs are flexible, play the important role of shock absorbers and ensure the spine movement and stability. The natural curvature of the spine is convex in the cervical part (lordotic curve), concave in the thoracic part (kyphotic curve) and convex again in the lumbar part (Figure 1). It is known that back pain is a major common public health problem. It impairs the quality of life, it represents one of the major cause of disability and is responsible for a large share of the healthcare costs. Approximatively 70 to 80% of the general population will encounter in its lifetime at least one episode of back pain. As a consequence, 1 to 2% of the gross national product will be engulfed in the healthcare and social costs, three times more than for cancer.1 The pain is said to be chronic when it lasts more than several weeks. The thresholds retained in the literature vary but are often set at 6 weeks for acute pain, between 6 and 12 weeks for subacute pain and 12 weeks for chronic pain.2, 3 The survey results of the Belgian Health interview survey 2013 show that 21% of Belgians aged 15 years or more suffered from low back disorder or other chronic back defect in the past 12 months and 12% from neck disorder or other chronic neck defect in the same period.4

8


Figure 1 – Anatomy of the spine

When the pain stays refractory to conservative treatment, surgery is often considered, consisting of discectomy with (as in the Belgian practice) or without fusion. After the removal of the diseased intervertebral disc (discectomy), the fusion consists in fastening the two vertebral bodies together, suppressing any spine mobility at this level. A possible alternative is a total disc replacement (TDR) during which the natural disc is replaced by a non-rigid artificial disc prosthesis without fastening the vertebrae together. The aim of the present report is to clarify the claimed advantages and disadvantages of these alternatives based on the evidence, on cervical level as well as on lumbar level.

1.2

http://commons.wikimedia.org/wiki/File:Spine_Anatomy_Kisco.JPG Although its exact cause remains unclear, degenerative disc disease (DDD) is often associated to chronic low back pain.5 The first step of spinal degenerative disease is thought to be intervertebral disc disease, typically followed by osteophytes, disc narrowing and spinal stenosis.6 The cervical and the lumbar spine are the most affected parts of the spine.7 Degenerative disc disease of the cervical spine can result in significant pain, instability, radiculopathy, myelopathy or a combination of symptoms.8 When lumbar spine is affected by DDD, the most common symptom is low back pain.

KCE Report 254

Scope and objectives

The research questions are the following: 1. What is the evidence of the short-term and long-term clinical effectiveness, safety and cost-effectiveness of total cervical disc replacement versus conservative treatment and/or (discectomy and) fusion in subacute/chronic radicular arm pain? 2. What is the evidence of the short-term and long-term clinical effectiveness, safety and cost-effectiveness of total lumbar disc replacement versus conservative treatment and/or (discectomy and) fusion in chronic lumbar pain due to intervertebral disc disorder? The report also describes the Belgian use and reimbursement of cervical (CTDR) and lumbar (LTDR) total disc replacements. Organisational, legal, ethical or patient issues other than patient outcomes (patient satisfaction, quality of life) are not covered in this rapid HTA.

KCE Report 254


2 CERVICAL TOTAL DISC REPLACEMENT 2.1

Health problems

9

About 30% of symptomatic patients presenting cervical DDD do not respond to conservative treatments and may be considered to be candidates for cervical surgery.7

HTA CORE MODEL DOMAIN: CUR1

2.1.2

2.1.1

The conservative therapeutic arsenal includes rest, physical rehabilitation, muscle-relaxants, analgesics or non-steroidal anti-inflammatory medication, epidural and selective nerve roots injections.7, 9 When conservative treatment is not effective, generally after 6 weeks, cervical spine surgery may be performed. Anterior cervical discectomy and fusion (ACDF) is commonly used to treat symptomatic cervical degenerative disc disease (DDD).10, 13-15 During this procedure, the pressure on the spinal nerve roots is relieved (decompression), the diseased disc is anteriorly removed and the left empty space is fused using some material. This material can be pedicle screw fixations, plate systems or cages but can also include autologous bone (often from the iliac bone), allogeneic bone (from a human or animal donor) or bone graft substitutes and osteogenic factors.16 This fusion relieves the pain supposedly by definitively suppressing the range of motion of the spine at the level of the disc disease.

Population and condition

The main indication that declare patients refractory to conservative treatment likely to be candidates for cervical spine surgery - including cervical total disc replacement - is cervical radiculopathy either from disc herniation and/or osteophytes. In the natural process of aging, intervertebral discs begin to lose proteoglycans, leading to moisture loss.9 They lose their flexibility, elasticity, and shock absorbing characteristics and begin to collapse. Osteophytes (bone spurs), disc herniation, kyphosis or instability begin to develop causing the narrowing of the foramen. Radiculopathy occurs when the nerve roots are compressed due to those changes, possibly causing neck pain, radiating pain in the shoulder, the arm or even the hand, muscle weakness and/or numbness or tingling in fingers or hands. Other symptoms may include lack of coordination, especially in the hands. In myelopathy, the compression involves the spinal cord. Because neural transmission is impaired, symptoms that can appear include altered gait of balance, sphincter disturbances, weakness, numbness or clumsiness of the hand. Over time, symptoms may diminish, stabilize or worsen.9, 10 The number of persons aged 40 or older presenting radiographic evidence of cervical DDD secondary to spondylosis amounts to 60%.10 In the older age, some studies evoke a percentage by 65 years of nearly 95% of males and 70% of females.11 Fortunately degenerations are most often asymptomatic.9 When it is symptomatic, symptoms can include neck and arm pain associated with radiculopathy and myelopathy.10 According to a 2006 systematic review, the European one year prevalence of neck pain was estimated to be 26% (95% CI 13% to 39%). That means that one out of 4 European citizens experienced neck pain in the last 12 months. Adult population is more affected than children or elderly and women slightly more than men.12 This is higher than the results of the Belgian Health Interview survey 2013 that show that about 12% of Belgians aged 15 years or more suffered from neck disorder or other chronic neck defect in the last year (14.3% women and 9.1% men).4

2.2

Existing treatments

Description and technical characteristics

HTA CORE MODEL DOMAIN: TEC The primary rationale behind the insertion of a cervical artificial disc instead of a fusion is to reduce adjacent level disease incidence by maintaining motion of the spine and hence reducing loads in adjacent segments. Secondarily, there is no morbidity associated with an autograft site or due to allograft material. Limitations exist to total disc replacement like a known allergy to implant material, osteoporosis, fusion of an adjacent level, spondylosis or facet joint degeneration.13 Total disc replacement may entail short-term well-known complications as implant migration, heterotopic ossification (ossification around the implant outside the vertebra body where it is fixated) and may also entail long-term complications on which less data are available such as implant subsidence, loosening or migration, material failure, allergic reactions, systemic release of metallic ions, visceral or neurologic injuries and infection.13

10


After a decade of experimentations in the fifties, the first real human implantation of a cervical device was performed by Ulf Fernstrom in 1966 (after several lumbar implantations of a similar device). The device was a stainless steel ball bearing a prosthesis. Others also experimented his type of device but the high failure rate (subsidence, migration and adjacent level hypermobility) put a curb on the early enthusiasm, surrendering to arthrodesis.17 It was only in the eighties that the popularity of the lumbar prostheses put the cervical device in the forefront again, especially in Europe. Several prototypes were developed that gave birth to the currently used devices. First introduced as the Cummins-Bristol disc in 1989, the Frenchay cervical disc (named after a hospital in the UK) demonstrated more favourable results in 2002. This disc was a metal-on-metal ball and socket device in stainless steel and the ancestor of the current Prestige Disc, manufactured by Medtronic. An anchoring screw was fixed into both pieces to avoid migration.17, 18 A first RCT demonstrated promising results for the Prestige Disc compared to anterior cervical discectomy and fusion in 2004.19 Parallel to this UK story, the American Vincent Bryan developed the Bryan cervical disc in the nineties, consisting of two titanium alloy shells articulating with a plastic (polyurethane) core. Several European studies confirmed favourable results compared to fusion. The first Bryan cervical disc was implanted in Belgium in 2000 by Pr Jan Goffin.20 In France, Dr Thierry Marnay conceived the ball and socket design of the Prodisc-C, as the cervical version of the lumbar one. The first implantation was performed in 2002.17 Compared to cervical discectomy and fusion, the aim of the cervical prosthesis is to maintain the natural disc mobility, to keep the original spine alignment, the cervical lordosis (the curve of the nape of the neck) and the intervertebral height to improve function. The maintenance of mobility also presents the advantage of potentially avoiding the adjacent segment degeneration that can occur after a fusion.9 Like the cervical discectomy and fusion, the total cervical disc replacement is performed by orthopaedic surgeons or neurosurgeons. The approach of a cervical prosthesis implantation is close to the anterior discectomy and fusion technique. Under general anaesthesia, the patient lies in supine position. Once the diseased intervertebral disc is removed by

KCE Report 254

a small anterior incision in the neck and the neurological elements are decompressed if need be, the surgeon inserts the cervical disc prosthesis into the intervertebral space instead of fusing the vertebrae. The centring of the device via fluoroscopy is crucial to the good functioning, mobility and probably reduced wear of the prosthesis.9, 21 Cervical artificial prostheses differ by their anchoring system (e.g. screws), the material of the bearing surface (e.g. metal, ceramic), the coating (e.g. porous mineral compound to ensure anchoring), the constraint (the degree to which it allows movement other than uniaxial rotation)16 their rotation centre (centre of disc, vertebral body) and their MRI compatibility (CoCrMo shows more artefacts on MRI rather than polymer or titanium).16, 21 A same model of prosthesis comes in different sizes and heights to fit all patients. Most materials of cervical (and lumbar) artificial discs have been widely used for many years in other orthopaedic prostheses (e.g. artificial hip and knee devices).7 Manufacturers also provide surgery kits dedicated to their branded cervical disc, those kits being different from the fusion material. The motions available to the spinal column are flexion and extension, lateral flexion and rotation (translations are also possible, increasing in amplitude from C2 to C7). Motions are said to be coupled as movements around two axes are involved to obtain a certain motion. Hence, pure lateral flexion and pure rotation do not occur. Gliding and tilting of the vertebrae make motions possible. Intervertebral discs increase the possibility of motion by separating two vertebrae and transmit load from one vertebra to another. They are present between vertebrae of the C2-C7 region.22 In this region, the surfaces of the vertebrae are not flat but rather curved in the sagittal plane.23 Simplifying the complex motion process of the normal cervical intervertebral discs, the cervical prosthesis can present up to 6 degrees of freedom in its movements: 3 in translation and 3 in rotation (along the three axes: vertical, transverse and sagittal). This is the case for what is called non-constraint devices, whereas semi-constraint devices including a mobile core have 5 degrees of freedom (2 in translation and 3 in rotation). Constraint devices, on the other hand, have only three degrees of freedom (no translation and 3 degrees in rotation).21The appealing unconstrained character may present a disadvantage such as inducing kyphosis.16, 21 The instantaneous centre of rotation of a cervical intervertebral disc is located somewhere in the superior part of the inferior vertebra (the lower the vertebra, the higher this centre is located in the vertebral body depending on the ratio between translation and

KCE Report 254


rotation).23 This feature is mimicked by some artificial discs including those that have a superior convexity. Devices with an inferior convexity rotate from above the device instead of below. Other devices present a centre of rotation elsewhere: e.g. on the upper vertebral body, posteriorly or even in the centre of the device.21 The design of the prosthesis often includes teeth (cf. Prodisc-C NOVA hereunder) or keels (cf. Prodisc-C VIVO) to facilitate the short-term stability while the long-term stability is insured by osteo-integration (bony on growth) with surrounding vertebrae, facilitated by a porous coating of the external faces of the endplates. Hereunder are the main cervical artificial discs available in Belgium. Characteristics and pictures of the main cervical artificial discs available in Belgium can be found in Table 1 and Table 2. Table 1 gives the year when the North American Food and Drug Administration (FDA) (USA) approved each device (PMA is the pre-market approval decision required for the prosthesis before US marketing) and when the CE mark was authorized (this CE mark is required for the launching on the European market).

Bryan Probably the most implanted cervical disc prosthesis worldwide until now, the unconstrained Bryan cervical disc is made of two titanium pieces articulating with a polyurethane core. The porous titanium particles sprayed on the external convex plates insures a better bony on growth while anterior flanges prevent posterior migration of the device. The core that allows motion and shock absorption is surrounded by a flexible polyurethane membrane containing a sterile saline lubricant. The membrane prevents soft tissue on growth and wear debris migration. The centre of rotation is located in the centre of the prosthesis.

Prestige The Prestige cervical disc is originally a semi-constrained stainless steel device made of two components articulated by a ball and socket design. The ball is on top and the inferior part is concave, which places the centre of rotation above the device. Since 1999, the flat side of each component that are in contact with the vertebrae is roughened through a grit blasting process to facilitate bony on growth. Anterior screws anchor the device to the two neighbouring vertebral bodies above and below the disc. In the more recent

11

version, the screws have been replaced by two anterior rails (Prestige STLP) and stainless steel has been replaced by titanium ceramic composite (Prestige LP).

Pro-Disc C The Prodisc-C has two titanium plates coated by plasma-sprayed rough pure titanium particles to facilitate osteo-integration. The anchorage is also insured by three keels (model NOVA) or by multiple teeth (model VIVO). The hemispheric inlay is in ultra-high molecular weight polyethylene (UHMWPE) rotating on a cobalt chromium molybdenum (CoCrMo) alloy internal surface. The rotation centre is located below the inferior plate.

Mobi-C The Mobi-C is a semi-constrained metal-on-polyethylene device. The metal plates are made of a cobalt chromium alloy, with a roughened titanium surface coated by hydroxyapatite. Naturally present in bone, hydroxyapatite is a porous calcium-based mineral compound that encourages bony on growth. The anchorage is also insured by the inclined teeth that also make the insertion easier. The motion is made possible by the polyethylene core, flat on the bottom and convex in its superior part to mould the concave surface of the superior plate. The centre of rotation is thus located on the lower vertebra surface. Two lateral stops on the inferior endplate limit the movement of the core. Until now the Mobi-C is the only device that has been approved for one-level and two-level use (two prostheses implanted at the same time) by the FDA (since August 2013).

Baguera C Baguera C presents six degrees of freedom that are controlled in magnitude. Both titanium plates are coated with Diamolith, a diamond like-carbon titanium coating that avoids wear debris thanks to its hardness and increases the sliding of the nucleus. Anchoring is facilitated by the coating, the sloping anatomical shape of the plates and three fins on each of the plates. Shock absorption is ensured by the high density polyethylene mobile nucleus and the shape of the non-flat inferior endplate.

12


KCE Report 254

M6-C This unconstrained prosthesis is made of two titanium endplates coated with a titanium plasma spray for bony on growth, presenting each three keels for anchoring. The core is a polyurethane nucleus wrapped in an annulus made of woven UHMWPE fibre. The annulus allows axial compression and the annulus controls the range of motion in the six degrees of freedom. The shock-absorbing annulus is surrounded by a polyurethane sheath designed to minimize soft tissue on growth and debris migration, like the membrane of the Bryan cervical disc described above.

Table 1 – List of main cervical artificial discs available in Belgium Device

Manufacturer

Distributor in Belgium

Constraint

Bearing surface material

Centre of rotation FDA Pre Market CE Mark Approval approval

Bryan

Medtronic

Medtronic

Unconstrained

Metal (Ti) on polyurethane

Centre of the disc

Prestige

Medtronic

Medtronic

Semi-constrained

Metal on metal, lately Ti Ceramic

Prodisc-C

Depuy Synthes*

Depuy Synthes*

Constrained

Mobi-C

LDR Medical

LDR Medical

Baguera C

Spineart

M6 C

Spinekinetics

2009

2000

Upper vertebra surface, posterior

2007

2002

Metal (CoCrMo) on polyethylene

Lower vertebra surface, posterior

2007

2002

Semi-constrained

Metal (CoCr) on polyethylene

Lower vertebra surface

2013

2004

HOSPITHERA

Semi-constrained

Metal (Ti) on polyethylene

Lower vertebra surface

No**

2007

Cormed

Unconstrained

Metal (Ti) on polyurethane

Centre of the disc

No**

2005

Adapted from Sekhon.16 * Depuy and Synthes were merged in 2012, as a company by Johnson & Johnson. ** Currently not marketed in the USA.

KCE Report 254


13

Table 2 – Pictures of main cervical artificial discs widely available in Belgium Bryan

Prestige LP

Prodisc-C: NOVA (left) and VIVO (right) models

Mobi-C

Baguera C

M6 C

Note: scale is not preserved between models.

14


Many other models are currently available from manufacturers from all over the world but their sales are anecdotical or inexistent in Belgium (situation in November 2014). They include prostheses with a ball and socket design composed of two metal plates rotating thanks to a convex core such as Discocerv (Scient’X-Alphatech Spine) distributed by Orthogèse, activ C (aesculap) by B. Braun Medical or SECURE-C (Globus Medical); prostheses with a poly-ether-ethyl-ketone (PEEK) ball and socket design like the NuNec (rti surgical formerly Pioneer Surgical Technology) by Inspine Belgium; prostheses with a ceramic ball and socket design like the GRANVIA C (MEDICREA) by Cormed, prostheses designed with two metallic endplates fitted together such as CerviCore (Stryker), Mobile Cervical Disc (Osteon), but also non-constrained prostheses like the UFO (BIOMECH Paonan Biotech Co., Ltd.) by Cormed, consisting of two dome-shaped metal plates hemming a load absorbing core and the polymeric one piece prostheses Cadisc-C (Ranier) by Inspine Belgium and Almas (Novaspine).

Belgian recommendations of good practice for cervical disc replacement The 2008 Belgian Society of Neurosurgery Recommendations of good practice considered the following situations to be acceptable for cervical disc replacement:24 

Age between 18 and 60, and



radiculopathy due to soft disc herniation and/or moderate uncarthrosis;

 1 or 2 levels maximum Additionally, none of the following contraindications should be found 

Severe uncarthrosis.



Severe facet arthritis.



Clinical or radiological myelopathy with exception of myelopathy due to a big soft herniation in combination with a sufficiently large spinal canal.



Spinal canal narrowing.

 Fracture. According to the experts group accompanying this study (see colophon), other contra-indications are considered in practice: infection, osteoporosis, radiographic instability, segmental or global deformity.

KCE Report 254

Belgian regulation and reimbursement Device The artificial cervical disc is currently not reimbursed in Belgium. Currently prices of a complete artificial cervical disc turn around €2500. Procedure The cervical total disc replacement is billed under one of the following INAMI – RIZIV nomenclature codes: 

281105 Cervical interbody arthrodesis, including the graft taking, or

 281120 Surgical treatment of a cervical disc herniation. In both cases, the reimbursed tariff amounts to €793.7 (N 625). These codes are not specific to the total disc arthroplasty, the first one can also be billed for a fusion. More details can be found in the appendix where one day surgery codes are also given (contrary to some surgeons abroad as in the USA for example, Belgian surgeons do not perform CTDR in one day hospitalisation setting).

2.3

Current use

HTA CORE MODEL DOMAIN: CUR2

2.3.1

Methods Data sources

To estimate the number of cervical artificial discs implanted in Belgium, we used three different sources of data: two administrative databases supplemented by the input from the industry via UNAMEC. The first administrative database is the Résumé Hospitalier Minimum – Minimum Ziekenhuisgegevens (RHM – MZG) managed by the Service Public Fédéral Santé publique, Sécurité de la Chaîne alimentaire et Environnement – Federale Overheidsdienst Volksgezondheid, Veiligheid van de Voedselketen en Leefmilieu (SPF – FOD), ensuing from the mandatory registration of all hospitalisations in every general nonpsychiatric Belgian hospital since 1991. Patient information are recorded in this administrative database, such as year of birth, gender, residence as well as other information about the stay in the hospital such as length of stay,

KCE Report 254


ICD-9-CM diagnostic codes of relevant diagnoses present on admission or appearing during hospitalisation and ICD-9-CM procedure codes of diagnostic and therapeutic procedures performed during the stay. After stripping direct patient-identifying information, records have to be sent twice a year to the SPF – FOD. As CTDR is only performed in hospital setting, we extracted the hospitalisations discharged between 2008 and 2011 (last available year in November 2014) presenting an ICD-9-CM procedure code 84.62 Insertion of total spinal disc prosthesis, cervical or 81.02 Other cervical fusion, anterior technique for ACDF. Selecting the fusions also allowed us to compare both populations. The INAMI – RIZIV houses the second administrative data we used. Since 1st of May 2009, every CE-marked implant and invasive medical device must be notified to the INAMI – RIZIV by the distributor, whether the product is reimbursable or not. Reimbursable devices must be notified to be reimbursed. A notified product receives an identification code. For nonreimbursable devices, such as cervical prostheses, this identification code must be written on the patient bill of the implanting hospital in order to be legally charged to the patient. UNAMEC is the Belgian federation counting more than 200 firms in the medical technology field that covers 80% of the market. There are only a few firms that do not belong to UNAMEC and sell a few cervical prostheses a year. This federation launched a survey in November 2014 asking their members to send us the number of cervical prostheses sold in the last two years.

Analysis We describe the current use of CTDR using simple descriptive statistics. After checking the normality, age at admission was compared between CTDR group and ACDF group using a t test, gender proportion using a χ² test and right skewed length of stay using a nonparametric Mann Whitney test.

2.3.2

15

Results Number of cervical prostheses implanted in Belgium

Table 3 – Number of cervical artificial discs or cervical total disc replacements by data source Source

Type of data

2008

2009

2010

2011

2012

2013

UNAMEC

Cervical artificial discs sales

-

-

-

-

635

615

RHM – MZG

Hospitalisations with CTDR coded in ICD-9-CM (84.62) and discharged in the year

570

479

485

443

-

-

INAMI – RIZIV

Cervical artificial discs notified on the patient bills

-

-

142(*)

548

471

481

(*) June-December.

Based on a survey organized by UNAMEC in November 2014, their members sold respectively 635 and 615 prostheses in 2012 and 2013 (Table 3). This number is higher than the number of the cervical prostheses notified to the INAMI – RIZIV and the procedures recorded in hospital discharges administrative database RHM – MZG. Obviously, per definition, sales may differ from actually implanted prostheses and there can be different time windows between procedures recorded in the hospital records and number of cervical artificial discs notified on the patient bills. For example, a procedure performed in 2008 can be recorded in RHM – MZG 2009. Nevertheless, figures should be from the same order of magnitude but several other factors may explain those remaining apparent discrepancies. Concerning the RHM – MZG, the number is probably underestimated. First, between 70 and 100 total disc replacements were coded each year using a nonspecific procedure ICD-9-CM code (84.60 Insertion of spinal disc prosthesis, not otherwise specified). Considering that total disc replacements in thoracic region are almost inexistent (± 3 a year), that partial disc replacements are much less frequent (33 cervical and lumbar

16


prostheses in 2011) and the ratio CTDR/LTDR increases over time (there were 240 lumbar procedures recorded for 2011 which meant 85% more cervical ones), most of those records can be attributed to the cervical region. Second, all hospitalisations during which at least one procedure was performed can be identified, but the number of times a procedure was performed, in the present matter the number of levels treated, is not a reliable variable and cannot be used. Hence, multi-level procedures are always counted once. The costs of a cervical prosthesis that is implanted without being notified must be borne by the implanting hospital. It can thus not be excluded that some prostheses are implanted but not notified which could theoretically lead to an underestimation of the implanted prostheses. The 2011 high figure could be attributed to the implementation of the new notification procedure for the firms as well as for the hospitals. In conclusion, we can estimate very roughly the number of cervical prostheses implanted in Belgium to range from 500 to 600 devices in 2013.

KCE Report 254

Figure 2 – Cervical total disc replacement: Age distribution per gender

Characteristics of patients undergoing cervical total disc replacement and comparison with patients undergoing a fusion Based on the hospitalisations recorded in the RHM – MZG database for the period 2008-2011, 56.8% of the 1977 implanted cases were female cases. On average patients were 45.8 year old (SD: 8.8, median: 46, range: 16-89). Figure 2 shows the age distribution per 5-year category per gender. Compared to three recent studies based on the USA Nationwide Inpatient Sample database using the same ICD-9-CM procedure codes, the proportion of women was higher in our data but the mean age was similar to their findings: 51.6% female cases and mean age of 46.4 year on 20022009 for Nandyala et al.,11 51.4% and 45.4 year on 2005-2008 for Nesterenko et al.,25 and 51.9% and 49.5 year on 2004-2007 for Qureshi et al.25, 26 All patients were admitted at least one night in the hospital. The mean length of stay amounted to 3.7 days (SD: 3.2, median: 3, range 1-73). Note that all patients were discharged alive. Length of stay appeared to be longer than what was observed in the USA (1.8,11 1.4,25 and 1.67 days26) where surgeons also operate in one day hospitalisation setting.

Source: RHM – MZG 2008-2011.

The most frequent principal diagnosis causing the admission was an intervertebral disc disorder (80.2% of the hospitalisations), followed by spondylosis (and allied disorders) (14.2%) or other disorders of the cervical region (3.8%). Inside the intervertebral disc disorder category, most of the cases suffered from a displacement of the cervical disc without myelopathy (50.6% of all hospitalisations). Others presented myelopathy (13%) and 13% had a cervical disc degeneration as principal diagnosis. The top 10 of the principal diagnosis in 3-digit ICD-9-CM codes, as well as the details of the first code split into 5-digit codes can be found in appendix. We also extracted the data of the patients who underwent a cervical fusion in order to compare their patient characteristics with those of the CTDR group. Because some hospitals also register a code of fusion in case of disc

KCE Report 254


replacement, we selected the 14 917 cases of fusion for whom no disc replacement was coded at all (neither partial nor total, whatever the location) and with a principal diagnosis of cervical intervertebral disc disorder (degeneration, displacement or other or unspecified disorder of the cervical intervertebral disc: ICD-9-CM codes 722.0, 722.4, 722.71 or 722.91). The 14 917 cases of ACDF included a few more male cases than the CTDR cases (45.7% versus 45.2%; p=0.0418) and were significantly older (49.3 year versus 45.8 year for CTDR group; p 20% of the scale, SMD > 0.7, RR < 0.5 or > 2.0. The majority of outcomes were suitable for a meta-analysis. Furthermore, no minimally clinically important difference (MCID) is established for cervical radicular pain in the literature which is one of the most important outcomes for the present comparison, and the expert group therefore agreed to utilize the above mentioned thresholds. However, it was noted by the experts that there are recent attempts to assess the MCID in pain, disability and quality of life after fusion.30 No MCID was defined for the outcomes such as mobility or ‘neurological success’ which were deemed not clinically relevant by the experts (see ‘neurological success’ in Table 5).

2.4.2

Results on Clinical Effectiveness

This chapter presents a review of the evidence on the clinical benefits of cervical total disc replacement (CTDR) versus fusion alone or fusion in combination with conservative treatment or versus conservative treatment alone. One relatively recent (search up to May 25th, 2011), very comprehensive and high quality Cochrane systematic review by Boselie et al.2 was identified and included early in the selection process.a This systematic review included a

On 20 May 2015, this systematic review was withdrawn due to noncompliance with The Cochrane Collaboration’s Commercial Sponsorship Policy. The impact of this decision on our own work can be considered as minor, since no publication bias was identified and because we also included an additional systematic review with longer follow-up period (i.e. 4 years; Ren

23

nine RCTs by Coric (2011), Heller (2009), Kelly (2011), Marzluff (2010), McAfee (2010), Mummaneni (2007), Nabhan (2007), Pettine (2010) and Porchet (2004). However, the Cochrane review only reported short-term (up to and including 3 months) and medium-term (one to two years) follow-ups and was restricted to single level CTDR compared to single level fusion. It was therefore important to assess whether we could identify additional systematic reviews with: 

A more recent search date (in particular if the systematic review had included primary studies that were not already included in the Cochrane review).



A longer follow-up period.



An inclusion of multi-level CTDR studies.



A comparison between CTDR and prolonged conservative treatment (> 6 weeks). Several more recent systematic reviews were identified. However, after a quality assessment it was decided to retain only one additional systematic review: 

A review by Ren31 with a search date up to March 2013, because this review reports on trials with a minimum of 48 months follow-up, and has a large number of outcomes identified as important for this review. In this process we also considered a review by Luo32 because this review has a very recent search date (April 2014) and therefore includes RCTs that are not included in other systematic reviews. However, there were considerable inconsistencies in the numbers reported in some of the metaanalyses within this review to an extent where it was deemed necessary to exclude this paper. The two systematic reviews retained2, 31 both reported results for clinical effectiveness but at different time-points.

2014) and recent RCTs published after the search date of Boselie. Results reported by original RCTs included in both systematic reviews (Boselie, 2012; Ren 2014) and by recent RCTs were pooled for each outcome under study. Our conclusions are based on these meta-analyses performed by the author of this chapter (KH).

24


Results from the two systematic reviews are presented below by outcome (domain) and subsequently by time-period (Cochrane review at outcomes after 3 months and at 12-24 months, and the Ren review on outcomes after ≥ 48 months). Please note that the review by Ren has reported mean difference results favouring CTDR as positive values in all their meta-analyses (e.g. a lower score in the CTDR group on the neck disability index is reported as a positive mean difference favouring CTDR, whereas the Cochrane review reports a similar mean difference favouring CTDR as a negative mean difference). For comprehensibility and readability we decided to report results in a similar way (practically this means that the result signs from the Ren review are reversed for outcomes such as functional status and pain). In cases where p-values were not provided but could be calculated or in cases where the statistics used to calculate p-values were doubtful, we used the Fischer Exact test to calculate the p-values ourselves. After the first experts meeting it was requested by some of the experts to add some more information on ASD, because they believe this is a very important outcome, and because the literature we initially included did not have this outcome as their main focus. We therefore searched for SRs specifically on this topic and added results from the most recent metaanalysis by Verma33 looking at the rate of ASD related surgery at 2 to 5 years to complement the information from the other SRs. Additionally, we searched for all randomised controlled trials that were not included in the retained systematic reviews with an aim to: 

search for RCTs on multi-level disease as well as RCTs comparing CTDR with prolonged conservative treatment. This process resulted in the selection of the following RCTs: Single level surgery (3 additional RCTs) An RCT by Vaccaro et al. from 201334 providing up to two-year results on clinical outcomes with selective constrained SECURE-C Cervical Disc TDR versus fusion. The trial included 380 patients. Unfortunately the trial had a non-inferiority design and the presentation of data and statistical methods used for assessing superiority could not be used to update meta-analysis (no MD, SD etc.).

An RCT by Phillips et al. from 201335 with 416 patients providing up to two-year results on effectiveness and safety for Porous Coated Motion (PCM) Cervical Disc Arthroplasty versus fusion.



An RCT by Zhang from 201236 with 120 patients providing up to twoyear results on outcomes comparing Bryan Cervical Disc Arthroplasty with fusion. We also considered but finally not retained 2 other RCTs: 

An RCT by Cheng.37 However, this small RCT with a total of 83 patients was of low quality, mixed single level surgery patients with multi-level (2 and 3 levels) patients without reporting outcomes for the two groups separately, and we therefore decided not to include this trial.



An RCT by Skeppholm from 201338 with 136 patients providing up to two-year results on a comparison of dysphagia between cervical disc replacement (with the Discover Artificial Disc) and fusion. Similarly, this RCT included data from both single-level and two-level surgery patients without properly reporting outcomes for the two groups separately, and we therefore also decided not to include this trial.

Multiple level surgery (2 additional RCTs) 

update the results from the systematic reviews,







KCE Report 254

An RCT by Davis et al.39 with 330 patients comparing CTDR (with the Mobi-C disc) with fusion for 2-level symptomatic disc disease (C3-C7). Patients were randomised in a 2:1 ratio (CTDR patients to fusion patients). The trial had a follow-up at 6 weeks, 3, 6, 12, 18, 24 and 48 months. The results after 3 months, 12 months, 24 months and 48 months are presented by outcome below.



An RCT by Cheng et al.40 with 65 patients suffering from two-level cervical disc disease (C3-4 to C6-7) comparing CTDR (with the Bryan Cervical Disc Replacement) with fusion. The trial had a follow-up at 1 week, 3 weeks, 6 weeks, 3 months, 6 months, 12 months and 24 months after surgery. However, statistical group differences were only reported for functional outcomes after 12 and 24 months. The results are presented by outcome below. Total disc replacement versus prolonged conservative treatment 

No RCTs were identified for this comparison.

KCE Report 254


25

Additional meta-analyses

12-24 months

For the meta-analyses, we used fixed effects meta-analysis except for the range of motion (ROM) mean difference at 12-24 months (CTDR versus fusion), where a random effects meta-analysis was preferred due to the high heterogeneity between the studies (I²=95%).

The Cochrane systematic review found a significant difference between CTDR and fusion in favour of CTDR (MD -2.79; 95% CI -4.73 to -0.85). Clinical relevance was low, since the pooled effect size was small (< 10% of the scale). For this outcome and time-point it was possible to update this meta-analysis with data from one RCT by Zhang.36 As displayed in Figure 5 the effect remained with a significant difference between CTDR and fusion in favour of CTDR (MD -1.89; 95% CI -3.44 to - 0.35) but with low clinical relevance.

Quality of the evidence Boselie et al. provided a GRADE score by outcome: the quality of evidence was considered to be very low (patient satisfaction), low (arm pain, global mental score SF-36 MCS) or moderate (neck pain, functional status, neurological success and global physical score SF-36 PCS).2 Due either to the non-blinded nature of the supplementary RCTs, their small size and/or the incomplete outcome data for some of them we judged the quality of the supplementary body of evidence as low for CTDR versus fusion. Consequently, we did not provide a GRADE score for each outcome separately in the scope of this rapid review. Besides, if there are very severe problems for any factor of the GRADE scoring tool, RCT evidence may fall by two levels due to that factor alone anyway.41, 42

Results single-level disease Functional Status Both systematic reviews and the additional RCTs reported functional status using the Neck Disability Index (NDI), using a 0-100 scale (lower is better). 3 months The Cochrane systematic review found a significant difference between CTDR and fusion in favour of CTDR (MD -5.14; 95% CI -6.94 to -3.34). Clinical relevance was low, since the pooled effect size was small (< 10% of the scale).

26


KCE Report 254

Figure 5 – Functional status: 12-24 months NDI mean difference (cervical total disc replacement versus fusion)

Two additional recent RCTs by Philips and Vaccaro did not provide mean and SD values and could therefore not be incorporated in the update of the meta-analysis. However, the RCT by Philips35 with a total of 416 patients found that NDI scores significantly favoured CTDR with a mean change in CTDR group of 21.8 vs. 25.5 in the fusion group (p=0.029). The other RCT by Vaccaro34 with 380 patients did not find superiority for one group vs. another according to their protocol-specified success criteria (≥ 25% improvement in NDI scores). ≥48 months The systematic review by Ren found a significant difference between CTDR and fusion in favour of CTDR (MD 5.49; 95% CI 2.79 to 8.20; p0.05, however, no exact p-value was provided). The Cheng study did not report statistical differences for this time-point. Mobility In the included studies range of motion, measured in degrees, for each treated level was calculated quantitatively from lateral flexion/extension radiographs and anteroposterior right/left lateral bending radiographs. 3 months Numbers are not provided in the papers. 12 months Numbers are not provided in the papers.

KCE Report 254


24 months The Davis study39 found that in the fusion group the mean ROM values at 24 months were less than 1 degree for both treated segments in both lateral flexion/extension and lateral bending. In the CTDR group mean flexion/extension and lateral bending was maintained from baseline throughout study duration. At 24 months mean ROM was 10.1° (SD=5.9°) in flexion/extension and 5.6° (SD=3.3°) at the superior treated level. For the inferior treated level the ROM values were 8.3° (SD=5.3°) in flexion/extension and 5.4° (SD=3.3°) in lateral bending. The Cheng study40 found that average flexion-extension in the CTDR group was 7.9° and in the fusion group 0.5°, but no between group statistics are provided. 48 months In the Davis study39 on average the CTDR group maintained their baseline flexion/extension and lateral bending after 48 months without device failures observed. ROM in degrees are not provided in the paper for the fusion group but it can be assumed that they did not differ from the results at 24 months. The Cheng study did not report mobility for this time-point. Neurological outcomes The RCT by Davis39 defined “neurological success” as the absence of significant neurological deterioration determined by investigator conducted evaluation that included motor assessment of muscle strength, sensory assessments and reflex assessments. This outcome was not assessed by Cheng et al.40 3 months Numbers are not provided in the paper. 12 months Numbers are not provided in the paper. 24 months Significant difference between the two treatment groups in favour of CTDR with 5.6% of patients showing neurological deterioration in the CTDR group and 6.7% showing neurological deterioration in the fusion group (authors use the Farrington-Manning test to compare frequencies between groups

33

and on the basis of this test conclude there is a significant difference with p